October 27, 2018Open Access

Variability in metabolic parameters and risk of dementia: a nationwide population-based study

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Dementia (n=2930816). Intervention: High variability in four metabolic parameters (blood pressure, glucose, cholesterol, BMI) vs. No parameters of high variability. Primary outcome: Incident all-cause dementia (HR 1.73, 95% CI 1.60-1.88, p=<0.001).

Key Result

High variability in four metabolic parameters (blood pressure, glucose, cholesterol, and body mass index) increased the risk of all-cause dementia by 73% (HR 1.73) compared to having no parameters with high variability.

Study Design

Type

Cohort (n=2,930,816)

Structured PICO

Does high visit-to-visit variability in metabolic parameters (blood pressure, glucose, cholesterol, BMI) increase the risk of dementia in a general population without baseline metabolic diseases?

Population

2,930,816 adults aged ≥45 years in Korea without a history of dementia, hypertension, diabetes mellitus, or dyslipidemia who underwent ≥ 3 health examinations.

Intervention

High visit-to-visit variability (defined as the highest quartile of the coefficient of variation) in blood pressure, fasting glucose, total cholesterol, and body mass index.

Comparator

Subjects having no parameters of high variability (values in the lower three quartiles for all parameters).

Outcome

Newly diagnosed dementia (further classified as Alzheimer's disease, vascular dementia, or other dementia) during follow-up.hard clinical

There is a linear, dose-response association between the number of metabolic parameters with high visit-to-visit variability and the risk of incident dementia in the general population.

Main Result

Effect estimate: HR 1.73 (95% CI 1.60-1.88)

Absolute Event Rate: 6.38% vs 1.28%

p-value: p=<0.001

Limitations

Discrepancies between the actual diagnosis and the information recorded in the claim database
Lack of cognitive function testing or imaging data to assess dementia severity
Unknown factors influencing the variability of metabolic parameters might moderate the dementia risk
Association between variability of HDL and LDL cholesterol and dementia could not be explored due to insufficient follow-up
Exclusion of subjects with fewer than three health examinations or missing data might be a source of selection bias
Optimal method of calculating variability is unknown

Abstract

BACKGROUND: Variability in biological parameters has been reported to be associated with adverse health outcomes. We aimed to investigate the composite effect of the visit-to-visit variability in blood pressure, glucose, cholesterol, and body mass index on the risk of dementia. METHODS: A population-based cohort study including 2,930,816 subjects without a history of dementia, hypertension, diabetes mellitus, and dyslipidemia who underwent ≥ 3 health examinations was performed. The coefficient of variation (CV), standard deviation, and variability independent of the mean were calculated as variability indices. High variability was defined as having values in the highest quartile for each parameter. RESULTS: A total of 32,901 (1.12%) participants developed dementia, of which 74.4% and 11.0% were attributable to Alzheimer's disease and vascular dementia, respectively, during the median follow-up of 5.5 years. Individuals with higher variability of each parameter were at higher risk of future dementia. In the multivariable adjusted model, the hazard ratios and 95% confidence intervals of all-cause dementia were 1.22 (1.19-1.26) for one parameter, 1.39 (1.35-1.43) for two parameters, 1.54 (1.48-1.60) for three parameters, and 1.73 (1.60-1.88) for four parameters compared with subjects having no parameters of high variability measured as the CV. Consistent results were noted for Alzheimer's disease and vascular dementia, using other indices of variability and in various sensitivity and subgroup analyses. CONCLUSIONS: There was a linear association between the number of high variability parameters and risk of dementia. Reducing variability of metabolic parameters would be a target to preserve cognitive reserve in the general population.

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